RT Conference Proceedings
T1 Neural activity control of neural stem cells and SVZ niche response to brain injury
A1 Páez-González, Patricia
K1 Células madre neurales
AB Patricia Paez-GonzalezKuo Lab, Dept. of Cell Biology, Duke University Medical Center, NC,USA.Date: 11/16/2014Utilizing stem cells in the adult brain hold great promise for regenerative medicine. Harnessingability of adult neural stem cells (NSCs) to generate new neurons or other types of brain cells mayprovide much needed therapies for patients suffering from brain injuries or neuro-degenerativediseases such as Parkinson’s, Scizophrenia, or Alzheimer’s disease. However, the treatments thatinvolve stem cells are based in NSC transplantation and its efficiency is really low.The major barriers-to-progress in this area of research are immune-rejection of the implantedcells, faulty tumorogenic growth, but mainly, a faulty integration of the improper progeny. To avoid theproblems that accompany NSC transplantation, we wanted to explore whether a new approach focusedon “modulating” the brain’s own resident stem cells to produce the appropriate cells after brain damagewas possible. In order to determine if “in situ” stem cell therapy was plausible, we first had to determinewhether 1)Environment provides the right signals for the proper NSC function and generation of theappropriate progeny, 2) whether in vivo NCSs are capable to elaborate an appropriate response underdifferent brain requirements, and 3) whether directed modulation of Neural Stem Cells function ispossible.We found that using genetic alteration in only the neighboring ependymal cells has the profoundimpact of nearly eliminating new neuron production in the lateral ventricular neurogenic region.Secondly, we determined that cortical strokes that do not impact the neurogenic region induceproduction on TSP4+ astrocytes that migrate to the injury site to produce the scar that stops corticalbleeding. Thirdly, we have identified a novel cholinergic circuit that resides in the neurogenic region,and that optogenetic stimulation or silencing of acetylcholine neurons can robustly up or down-regulatenew neuron production. These three discoveries have met the required conditions for using intrinsicNSCs as therapy for brain regeneration and repair. I am now extending this line of research todetermine if this therapy is now a feasible technique for brain repair understanding how the local braincircuits are modified as the NSCs transition to an injury response and back to normal productionfollowing recovery. Together these data suggest that therapies utilizing the bodies own intrinsic controlmechanisms for NSC regulation may soon provide much needed avenues for future therapies that areunattainable with other methods.
YR 2014
FD 2014-11-25
LK http://hdl.handle.net/10630/8476
UL http://hdl.handle.net/10630/8476
LA spa
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 25 ene 2026